What psychiatric medications do not lower the seizure threshold?

Psychiatric Medications That Do Not Lower the Seizure Threshold

Benzodiazepines are the only class of psychiatric medications that do not lower the seizure threshold and may actually increase it, making them the safest option for patients with epilepsy or seizure risk. 1

Understanding Seizure Threshold and Psychiatric Medications

Seizure threshold refers to the level of neuronal excitation required to trigger a seizure. Many psychiatric medications can affect this threshold, potentially increasing seizure risk in vulnerable patients. This is particularly important when treating patients with:

• History of epilepsy
• Brain injury or structural abnormalities
• Previous seizures
• Family history of seizures
• Concurrent use of other medications that lower seizure threshold

Medications by Seizure Risk

Safe Options (Do Not Lower Seizure Threshold)

• Benzodiazepines (e.g., diazepam, lorazepam, clonazepam)
  • Actually increase seizure threshold 1
  • Can be used as anticonvulsants
  • May be preferred for anxiety disorders in patients with seizure risk

Low Risk Options

• Antipsychotics:

  • Haloperidol
  • Fluphenazine
  • Pimozide
  • Risperidone
  • Aripiprazole
  • Quetiapine
  • Amisulpride 2, 3

• Antidepressants:

  • Phenelzine
  • Tranylcypromine
  • Paroxetine
  • Sertraline 4

High Risk Options (Significantly Lower Seizure Threshold)

• Antipsychotics:

  • Clozapine (highest risk)
  • Chlorpromazine 4, 2, 3

• Antidepressants:

  • Maprotiline
  • Clomipramine
  • Bupropion 4

Risk Factors That Increase Seizure Potential

Several factors can increase the risk of medication-induced seizures:

• Rapid dose titration
• High doses
• Polypharmacy (especially multiple medications that lower seizure threshold)
• Metabolic factors (renal/hepatic impairment)
• Drug-drug interactions
• History of seizures or brain injury 3

Clinical Approach for Patients with Seizure Risk

When prescribing psychiatric medications to patients with seizure risk:

1. Start with benzodiazepines when clinically appropriate, as they raise seizure threshold
2. If other medications are needed, select those with lower seizure risk
3. Start with low doses and titrate slowly
4. Maintain the minimal effective dose
5. Avoid complex drug combinations
6. Monitor drug levels when applicable
7. Consider prophylactic anticonvulsants when using high-risk medications in vulnerable patients 5, 4

Special Considerations

• For psychosis: Consider risperidone, aripiprazole, or haloperidol rather than clozapine or chlorpromazine
• For depression: Consider sertraline or paroxetine rather than clomipramine or bupropion
• For anxiety: Benzodiazepines are preferred when appropriate

While some studies suggest certain SSRIs like fluoxetine may have antiseizure properties in specific populations 6, the overall evidence suggests caution with most psychiatric medications in seizure-prone individuals.